Because of their valuable therapeutic potential, testosterone 5-alpha-reductase inhibitors have been the subject of active research worldwide and have been disclosed in numerous publications, United States and International patents and International patent applications, for example see, Hsia, S. and Voight, W., J. Invest. Derm., 62, 224 (1973); Liang, T., et al., J. Steroid Biochem., 19, 395 (1983); Holt, D., J. Med. Chem., 33, 937 (1990); U.S. Pat. No. 4,377,584, to Rasmusson et al., issued Mar. 22, 1983, U.S. Pat. No. 5,017,568, to Holt et al., issued May 21, 1991, World patent applications WO 93/13124, filed by Glaxo Inc., and entitled, Inhibitors of 5-Alpha-Testosterone Reductase and WO 94/14833, field by Glaxo Inc., and entitled, Substituted 6-Azaandrostenones.
Previous methods used in the preparation of 6-azaandrostenones require the use of hazardous azide intermediates, extensive use of protecting groups which increase the number of synthetic steps, and the use of toxic heavy metal oxidants, for example see; Lettre, H., et al., Liebigs Ann. Chem 703, 147, (1967) and World Patent Application WO 93/13124, filed by Glaxo Inc., and entitled, Inhibitors of 5-Alpha-Testosterone Reductase. The present Invention provides a novel and efficient method for the preparation of useful intermediates, and 6-azaandrostenones of Formula (I) from commercially available compounds of Formula (II). The processes of the present Invention avoid the use of hazardous intermediates, and reagents, and are thus amenable to synthesis on a commercial scale.